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PMID: 10673499 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP.

Genes & development ·Vol. 14 ·No. 3 ·2000-02-01 ·Pages 272-7

Kung AL, Rebel VI, Bronson RT, Ch'ng LE, Sieff CA, Livingston DM, Yao TP

Abstract

Mice with monoallelic inactivation of the CBP gene develop highly penetrant, multilineage defects in hematopoietic differentiation and, with advancing age, an increased incidence of hematologic malignancies. The latter are characterized, at least in some cases, by loss of heterozygosity (LOH) at the CBP locus. No such pathology was observed in wild-type or p300 heterozygous null mice of the same age and genetic background. Thus, a full complement of CBP, but not p300, is required for normal hematopoietic differentiation. These results also provide the first experimental evidence for the hypothesis that CBP has tumor-suppressing activity.

MeSH Terms
Animals Blotting, Southern Blotting, Western Bone Marrow Transplantation CREB-Binding Protein Cell Transplantation E1A-Associated p300 Protein Genes, Tumor Suppressor/genetics Hematologic Neoplasms/genetics,pathology Hematopoiesis/genetics Heterozygote Loss of Heterozygosity Mice Mice, Inbred C57BL Mice, Knockout Nuclear Proteins/genetics,metabolism Phenotype Spleen/cytology Trans-Activators/genetics,metabolism
Chemicals
Nuclear Proteins Trans-Activators CREB-Binding Protein Crebbp protein, mouse E1A-Associated p300 Protein Ep300 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kung A L
Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rebel V I
Bronson R T
Ch'ng L E
Sieff C A
Livingston D M
Yao T P
References (32)
32 references, click to expand
  1. The transcriptional coactivators p300 and CBP are histone acetyltransferases.
    Cell. 1996 Nov 29;87(5):953-9 PMID: 8945521
  2. Identification of c-MYC as a target of the APC pathway.
    Science. 1998 Sep 4;281(5382):1509-12 PMID: 9727977
  3. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.
    Nat Genet. 1996 Sep;14(1):33-41 PMID: 8782817
  4. p300 and CBP as transcriptional regulators and targets of oncogenic events.
    Biol Chem. 1996 Nov;377(11):685-8 PMID: 8960368
  5. RNA helicase A mediates association of CBP with RNA polymerase II.
    Cell. 1997 Sep 19;90(6):1107-12 PMID: 9323138
  6. The morphology, immunohistochemistry, and incidence of hematopoietic neoplasms in mice and rats.
    Toxicol Pathol. 1993;21(2):206-18 PMID: 8210943
  7. p300 gene alterations in colorectal and gastric carcinomas.
    Oncogene. 1996 Apr 4;12(7):1565-9 PMID: 8622873
  8. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10626-31 PMID: 8855229
  9. Experimental plasmacytomagenesis in mice.
    Hematol Oncol Clin North Am. 1997 Apr;11(2):323-47 PMID: 9137973
  10. Genetic analysis of adenovirus E1A: induction of genetic instability and altered cell morphologic and growth characteristics are segregatable functions.
    Mutat Res. 1998 Oct 12;421(1):9-25 PMID: 9748479
  11. Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis.
    Blood. 1999 May 1;93(9):2771-9 PMID: 10216070
  12. Conjunction dysfunction: CBP/p300 in human disease.
    Trends Genet. 1998 May;14(5):178-83 PMID: 9613201
  13. Chromatin remodeling and leukemia: new therapeutic paradigms.
    Blood. 1999 Jul 15;94(2):417-28 PMID: 10397708
  14. The CBP co-activator is a histone acetyltransferase.
    Nature. 1996 Dec 19-26;384(6610):641-3 PMID: 8967953
  15. The molecular role of Myc in growth and transformation: recent discoveries lead to new insights.
    FASEB J. 1998 Jun;12(9):633-51 PMID: 9619443
  16. The adenovirus E1A-associated 300-kD protein exhibits properties of a transcriptional coactivator and belongs to an evolutionarily conserved family.
    Cold Spring Harb Symp Quant Biol. 1994;59:85-95 PMID: 7587135
  17. Essential role for the p55 tumor necrosis factor receptor in regulating hematopoiesis at a stem cell level.
    J Exp Med. 1999 Nov 15;190(10):1493-504 PMID: 10562323
  18. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.
    Nature. 1995 Jul 27;376(6538):348-51 PMID: 7630403
  19. Cellular targets for transformation by the adenovirus E1A proteins.
    Cell. 1989 Jan 13;56(1):67-75 PMID: 2521301
  20. Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling.
    Nature. 1998 Oct 1;395(6701):521-5 PMID: 9774110
  21. Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism.
    Hum Mol Genet. 1999 Mar;8(3):387-96 PMID: 9949198
  22. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A.
    Nature. 1996 Jul 25;382(6589):319-24 PMID: 8684459
  23. Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome.
    Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10215-20 PMID: 9294190
  24. Definition of adenovirus type 5 functions involved in the induction of chromosomal aberrations in human cells.
    J Gen Virol. 1990 Apr;71 ( Pt 4):801-8 PMID: 2139107
  25. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2061-6 PMID: 9482838
  26. The murine gene p27Kip1 is haplo-insufficient for tumour suppression.
    Nature. 1998 Nov 12;396(6707):177-80 PMID: 9823898
  27. MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3).
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8732-7 PMID: 9238046
  28. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
    Cell. 1997 Aug 22;90(4):595-606 PMID: 9288740
  29. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.
    Cell. 1998 May 1;93(3):361-72 PMID: 9590171
  30. Tumors in Rubinstein-Taybi syndrome.
    Am J Med Genet. 1995 Mar 13;56(1):112-5 PMID: 7747773
  31. Independent transformation activity by adenovirus-5 E1A-conserved regions 1 or 2 mutants.
    Virology. 1991 Jun;182(2):553-61 PMID: 1827227
  32. The p300/CBP family: integrating signals with transcription factors and chromatin.
    Trends Cell Biol. 1997 Jun;7(6):230-6 PMID: 17708951
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2000-02-01
Pages
272-7
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316359
Subset
IM
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